Mechanisms of blister formation in pemphigus foliacues analyzed by anti-Dsg1 monoclonal antibodies

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09749
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Toho University
• Principal Investigator: ISHII Ken 東邦大学, 医学部, 准教授 (50296670)
• Co-Investigator(Kenkyū-buntansha): 石河 晃 東邦大学, 医学部, 教授 (10202988)
• Research Collaborator: YOSHIDA Kenji
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 天疱瘡 / 自己抗体 / 細胞接着 / カドヘリン

Outline of Final Research Achievements

Pemphigus foliaceus (PF) is an autoimmune blistering disease caused by autoantibodies (Abs) against desmoglein 1 (Dsg1). PF sera contain polyclonal Abs which are heterogeneous mixture of both pathogenic and non-pathogenic Abs, as shown by isolation of monoclonal Abs (mAbs).The purpose of study is to investigate how pathogenic and non-pathogenic anti-Dsg1 Abs contribute to blister formation in PF.　Using organ-cultured human skin, we compared the effect of a single pathogenic anti-Dsg1 IgG mAb, a single non-pathogenic anti-Dsg1 IgG mAb, and their mixture on blister formation as analyzed by histology, subcellular localization of IgG deposits and desmosomal proteins by confocal microscopy. We found a polyclonal mixture of anti-Dsg1 IgG antibodies enhances pathogenic activity for blister formation associated with p38MAPK-dependent Dsg1 clustering and that not only pathogenic antibodies but also non-pathogenic antibodies coordinately contribute to blister formation in PF.

Free Research Field

皮膚科